A recent study has revealed that evolocumab add-on therapy is linked to a significant reduction in plaque in patients with intracranial atherosclerotic stenosis (ICAS) compared to statin therapy alone. Conducted over a six-month period, the trial highlights the potential of this treatment option to improve outcomes for individuals suffering from this condition.
The study builds on findings from previous research, notably the GLAGOV randomized clinical trial, which explored the effectiveness of evolocumab and other PCSK9 inhibitors in managing coronary atherosclerosis. The GLAGOV trial demonstrated that patients receiving evolocumab experienced lower mean time-weighted low-density lipoprotein cholesterol levels compared to those on a placebo.
Dr. Xinzhi Hu, a neurologist at the Peking Union Medical College Hospital, pointed out the limited focus on evolocumab’s effects on ICAS in existing literature. “In this study, we sought to investigate whether evolocumab add-on therapy over 6 months achieves more intracranial plaque burden reduction than statin alone in patients with ICAS,” he explained.
To conduct the study, researchers utilized a real-world high-resolution magnetic resonance imaging (HR-MRI) database established in 2015. They enrolled patients diagnosed with ICAS between 2016 and 2023, ensuring comprehensive evaluations through conventional cranial MRI, HR-MRI, and blood tests.
For inclusion, patients had to have confirmed ICAS (50%-99%) in specific arterial segments, with the condition attributed to atherosclerosis. They underwent two HR-MRI scans during the study and were on continuous oral lipid-lowering therapy, including statins and/or ezetimibe, with or without evolocumab.
Patients were excluded if they had concurrent significant extracranial vessel stenosis or if they had nonatherosclerotic intracranial artery stenosis, among other criteria. The primary endpoint of the study was assessed as plaque response, defined as plaque regression greater than 5%. Secondary endpoints included changes in plaque burden and the degree of stenosis.
A total of 179 patients participated in the trial, with 50 receiving evolocumab in addition to statin therapy and 129 serving as the control group. Findings revealed a notable difference in outcomes: the evolocumab cohort exhibited a higher plaque response rate of 68% compared to 34.1% in the control group. Additionally, the median reduction in plaque burden was significantly greater in the evolocumab group at -8.2% versus -1.9%. The reduction in the degree of stenosis also favored the evolocumab cohort, with a decrease of -15.3% compared to -5.4%.
The adjusted regression analysis further confirmed the strength of these associations. Evolocumab usage correlated with a plaque response odds ratio of 6.67 and a 7% reduction in plaque burden. Subgroup analyses based on statin intensity also supported these findings.
“These preliminary findings suggest that this combination therapy may offer a potentially more effective strategy for reversing intracranial atherosclerotic plaque,” Dr. Hu and colleagues stated. They emphasized the need for further prospective, randomized controlled studies to validate these results and explore their clinical implications.
This research, published in the Journal of the American Heart Association, marks a significant advancement in understanding the role of evolocumab in treating ICAS, paving the way for potential new treatment protocols in the future.
